A magnetic resonance imaging-based lymph node regression grading scheme for nasopharyngeal carcinoma after radiotherapy.

Background: Among patients with nasopharyngeal carcinoma (NPC), there is no established method to distinguish between patients with residual disease that may eventually progress and those who have achieved cured. We thus aimed to assess the prognostic value of magnetic resonance imaging (MRI)-based lymph node regression grade (LRG) in the risk stratification of patients with NPC following radiotherapy (RT). Methods: This study retrospectively enrolled 387 patients newly diagnosed with NPC between January 2010 and January 2013. A four-category MRI-LRG system based on the areal analysis of RT-induced fibrosis and residual tumor was established. Univariate analysis was performed using the Kaplan-Meier method, and comparisons were conducted via the log-rank test. Multivariate analyses were conducted using Cox regression models to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted P values. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: The sum of MRI-LRG scores (LRG-sum) was an independent prognostic factor for progression-free survival (PFS) (HR 2.50, 95% CI: 1.28-4.90; P<0.001). LRG-sum ≤9 and >9 showed a poorer 5-year PFS rate than did LRG-sum ≤2 (66.1%, 42.9%, and 77.6%, respectively; P<0.001). A survival clustering analysis-based decision tree model showed more complex interactions among LRG-sum and pretreatment and post-RT Epstein-Barr virus (EBV) DNA, yielding four patient clusters with differentiated disease progression risks (5-year PFS rates of 89.5%, 76.4%, 57.6%, and 27.8%, respectively), which showed better risk stratification than did post-RT EBV DNA alone (P<0.001). Conclusions: The MRI-LRG system adds prognostic information and is a potentially reliable, noninvasive means to stratify treatment modalities for patients with NPC.

Sulfur oxidation states manipulate excited state electronic configurations for constructing highly efficient organic type I photosensitizers.

The multiple relaxation processes of excited states are a bridge connecting molecular structures and properties, providing enormous application potential for organic luminogens. However, a systematic understanding and manipulation of the relationship between the molecular structure, excited state relaxation processes, and properties of organic luminogens is still lacking. Herein, we report a strategy for manipulating excited state electronic configurations through the regulation of the sulfur oxidation state to construct eminent organic type I PSs. Combined with the experimental results and theoretical calculations, we have successfully revealed the decisive role of high sulfur oxidation states in promoting ROS production capacity. Impressively, a higher sulfur oxidation state can reduce the singlet-triplet energy gap (ΔE ST), increase the matching degree of transition configurations, promote the changes of the excited state electronic configurations, and boost the effective ISC proportion by enhancing intramolecular interactions. Therefore, DBTS2O with the highest sulfur oxidation state exhibits the strongest type I ROS generation ability. Additionally, guided by our strategy, a water-soluble PS (2OA) is designed and synthesized, showing selective imaging capacity and photokilling ability against Gram-positive bacteria. This study broadens the horizons for both molecular design and mechanism study of high-performance organic type I PSs.

Automated segmentation of brain metastases with deep learning: a multi-center, randomized crossover, multi-reader evaluation study.

BACKGROUND: Artificial intelligence has been proposed for brain metastasis (BM) segmentation but it has not been fully clinically validated. The aim of this study was to develop and evaluate a system for BM segmentation. METHODS: A deep-learning-based BM segmentation system (BMSS) was developed using contrast-enhanced MR images from 488 patients with 10,338 brain metastases. A randomized crossover, multi-reader study was then conducted to evaluate the performance of the BMSS for BM segmentation using data prospectively collected from 50 patients with 203 metastases at five centers. Five radiology residents and five attending radiologists were randomly assigned to contour the same prospective set in assisted and unassisted modes. Aided and unaided Dice similarity coefficients (DSCs) and contouring times per lesion were compared. RESULTS: The BMSS alone yielded a median DSC of 0.91 (95% confidence interval, 0.90-0.92) in the multi-center set and showed comparable performance between the internal and external sets (p = 0.67). With BMSS assistance, the readers increased the median DSC from 0.87 (0.87-0.88) to 0.92 (0.92-0.92) (p < 0.001) with a median time saving of 42% (40-45%) per lesion. Resident readers showed a greater improvement than attending readers in contouring accuracy (improved median DSC, 0.05 [0.05-0.05] vs. 0.03 [0.03-0.03]; p < 0.001), but a similar time reduction (reduced median time, 44% [40-47%] vs. 40% [37-44%]; p = 0.92) with BMSS assistance. CONCLUSIONS: The BMSS can be optimally applied to improve the efficiency of brain metastasis delineation in clinical practice.

Deep learning model based on contrast-enhanced MRI for predicting post-surgical survival in patients with hepatocellular carcinoma.

Objective: To develop a deep learning model based on contrast-enhanced magnetic resonance imaging (MRI) data to predict post-surgical overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: This bi-center retrospective study included 564 surgically resected patients with HCC and divided them into training (326), testing (143), and external validation (95) cohorts. This study used a three-dimensional convolutional neural network (3D-CNN) ResNet to learn features from the pretreatment MR images (T1WIpre, late arterial phase, and portal venous phase) and got the deep learning score (DL score). Three cox regression models were established separately using the DL score (3D-CNN model), clinical features (clinical model), and a combination of above (combined model). The concordance index (C-index) was used to evaluate model performance. Results: We trained a 3D-CNN model to get DL score from samples. The C-index of the 3D-CNN model in predicting 5-year OS for the training, testing, and external validation cohorts were 0.746, 0.714, and 0.698, respectively, and were higher than those of the clinical model, which were 0.675, 0.674, and 0.631, respectively (P = 0.009, P = 0.204, and P = 0.092, respectively). The C-index of the combined model for testing and external validation cohorts was 0.750 and 0.723, respectively, significantly higher than the clinical model (P = 0.017, P = 0.016) and the 3D-CNN model (P = 0.029, P = 0.036). Conclusions: The combined model integrating the DL score and clinical factors showed a higher predictive value than the clinical and 3D-CNN models and may be more useful in guiding clinical treatment decisions to improve the prognosis of patients with HCC.

Histogram analysis of MR quantitative parameters: are they correlated with prognostic factors in prostate cancer?

PURPOSE: To investigate the correlation between quantitative MR parameters and prognostic factors in prostate cancer (PCa). METHOD: A total of 186 patients with pathologically confirmed PCa who underwent preoperative multiparametric MRI (mpMRI), including synthetic MRI (SyMRI), were enrolled from two medical centers. The histogram metrics of SyMRI [T1, T2, proton density (PD)] and apparent diffusion coefficient (ADC) values were extracted. The Mann‒Whitney U test or Student's t test was employed to determine the association between these histogram features and the prognostically relevant factors. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the differentiation performance. Spearman's rank correlation coefficients were calculated to determine the correlations between histogram parameters and the International Society of Urological Pathology (ISUP) grade group as well as pathological T stage. RESULTS: Significant correlations were found between the histogram parameters and the ISUP grade as well as pathological T stage of PCa. Among these histogram parameters, ADC_minimum had the strongest correlation with the ISUP grade (r = - 0.481, p < 0.001), and ADC_Median showed the strongest association with pathological T stage (r = - 0.285, p = 0.008). The ADC_10th percentile exhibited the highest performance in identifying clinically significant prostate cancer (csPCa) (AUC 0.833; 95% CI 0.771-0.883). When discriminating between the status of different prognostically relevant factors, a significant difference was observed between extraprostatic extension-positive and -negative cancers with regard to histogram parameters of the ADC map (10th percentile, 90th percentile, mean, median, minimum) and T1 map (minimum) (p = 0.002-0.032). Moreover, histogram parameters of the ADC map (90th percentile, maximum, mean, median), T2 map (10th percentile, median), and PD map (10th percentile, median) were significantly lower in PCa with perineural invasion (p = 0.009-0.049). The T2 values were significantly lower in patients with seminal vesicle invasion (minimum, p = 0.036) and positive surgical margin (10th percentile, 90th percentile, mean, median, and minimum, p = 0.015-0.025). CONCLUSION: Quantitative histogram parameters derived from synthetic MRI and ADC maps may have great potential for predicting the prognostic features of PCa.

Metabolic dysfunction-associated steatotic liver disease-related hepatic fibrosis increases risk of insulin resistance, type 2 diabetes, and chronic kidney disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) (previously called nonalcoholic fatty liver disease, NAFLD) is associated with cardiometabolic risk factors and chronic kidney disease (CKD). However, evidence is lacking regarding whether the severity of fibrosis is affected by these risk factors and diseases and to what degree. We aimed to determine the correlation between these factors and vibration-controlled transient elastography-determined liver stiffness measurements (LSMs) and controlled attenuation parameter (CAP) values in a sample of the US population. Data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey were pooled. The association between LSM and cardiometabolic risk factors and CKD was assessed using generalized linear or logistic regression analyses. In multivariate regression analyses, CAP and BMI were adjusted as confounders. Of 3647 participants, 2079 (57.1%) had NAFLD/MASLD [weighted prevalence 54.8%; 95% confidence interval (CI) 51.8-57.9%]; the weighted prevalence of significant fibrosis (LSM ≥ 7.9 kPa) was 9.7% (95% CI 8.2-11.3%). Log LSM was associated with higher levels of homeostatic model assessment of insulin resistance ( ß â€…= 2.19; P  = 0.017), hepatic steatosis (CAP > 248 dB/m) [odds ratio (OR) 3.66; 95% CI 2.22-6.02], type 2 diabetes (OR 2.69; 95% CI 1.72-4.20), and CKD (OR 1.70; 95% CI 1.24-2.34). These correlations did not change notably after adjustments were made for waist circumference, CAP, and BMI. LSM and CAP, although influenced by waist circumference and BMI, are good indicators of hepatic fibrosis and steatosis. LSM is associated with insulin resistance, diabetes, and CKD independent of hepatic steatosis and obesity.

Pyrroloquinoline Quinone Improves Ram Sperm Quality through Its Antioxidative Ability during Storage at 4 °C.

Sperm motility is an important factor in the migration of sperm from the uterus to the oviduct. During sperm preservation in vitro, sperm generates excessive ROS that damages its function. This study aims to investigate whether the addition of pyrroloquinoline quinone (PQQ) to the diluted medium could improve chilled ram sperm quality, and then elucidates the mechanism. Ram semen was diluted with Tris-citric acid-glucose (TCG) medium containing different doses of PQQ (0 nM, 10 nM, 100 nM, 1000 nM, 10,000 nM), and stored at 4 °C. Sperm motility patterns, plasma membrane integrity, acrosome integrity, mitochondrial membrane potential, reactive oxygen species (ROS) levels, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and ATP levels were measured after preservation. Furthermore, the expressions of NADH dehydrogenase 1 (MT-ND1) and NADH dehydrogenase 6 (MT-ND6) in sperm were also detected by western blotting. In addition, sperm capacitation and the ability of sperm to bind to the zona pellucina were also evaluated. It was observed that the addition of PQQ significantly (p < 0.05) improved ram sperm motility, membrane integrity, and acrosome integrity during preservation. The percentage of sperm with high mitochondrial membrane potential in the PQQ treatment group was much higher than that in the control. In addition, supplementation of PQQ also decreased the sperm MDA and ROS levels, while increasing ATP levels. Interestingly, the levels of MT-ND1 and MT-ND6 protein in sperm treated with PQQ were also higher than that of the control. Furthermore, the addition of 100 nM PQQ to the medium decreased ROS damage in MT-ND1 and MT-ND6 proteins. The addition of 100 nM PQQ significantly (p < 0.05) increased protein tyrosine phosphorylation in ram sperm after induced capacitation. Furthermore, the value of the sperm-zona pellucida binding capacity in the 100 nM PQQ treatment group was also much higher than that of the control. Overall, during chilled ram- sperm preservation, PQQ protected ram sperm quality by quenching the ROS levels to reduce ROS damage and maintain sperm mitochondrial function, and preserved the sperm's high ability of fertilization.

N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation.

BACKGROUND: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS: Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

Factors predicting depressive symptoms in parents of children with autism spectrum disorder in eastern China.

BACKGROUND: Parents of children with autism spectrum disorder (ASD) are at a higher risk of depression than parents of typically developing children and those of children with other developmental disorders. Depression affects the well-being and quality of life of parents of children with ASD and has serious consequences for the long-term health outcomes of children with ASD. Therefore, this study explored the current status of depressive symptoms in parents of children with ASD in eastern China and further analyzed multiple aspects of the predictors of depressive symptoms. METHODS: A multicenter cross-sectional survey was conducted among parents of children with ASD in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China. A structured questionnaire that focused on child-related factors, parent-related factors, depressive symptoms, courtesy stigma, and social support was used to obtain data. Binary logistic regression was used to identify the independent predictors of depressive symptoms in parents of children with ASD. RESULTS: A total of 409 parents of children with ASD were recruited, of whom 18.8% had depressive symptoms. Parents of children with ASD who raised a child who spoke few to no words (odds ratio [OR]: 2.747, 95% confidence interval [CI]: 1.026-7.357), claimed a high economic burden (OR: 3.215, 95% CI: 1.234-8.379), reported no change or increased severity of ASD in their children (OR: 2.518, 95% CI: 1.108-5.720), and those with a higher courtesy stigma score (OR: 1.189, 95% CI: 1.093-1.294) were more likely to have depressive symptoms. Conversely, parents of children with ASD who were employed (OR: 0.427, 95% CI: 0.201-0.907), satisfied with their current marital status (OR: 0.429, 95% CI: 0.221-0.834), and those with a higher social support score (OR: 0.973, 95% CI: 0.950-0.996) were less likely to have depressive symptoms. CONCLUSIONS: Depressive symptoms are common in parents of children with ASD in eastern China. Therefore, screening and intervention for depressive symptoms in parents of children with ASD is necessary, especially for those with high-risk factors.

Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors.

Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with anti-tumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/ refractory mature B-cell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase II dose (RP2D) (clinicaltrials gov. Identifier: NCT02857998). Overall, 134 Chinese patients were enrolled (dose escalation, N=27; dose expansion, N=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d.), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d.. The primary efficacy end point of independent review committee-assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% confidence interval: 37.5- 64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the dose-expansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased dose-proportionally with ascending dose levels from 200-800 mg, without observed saturation. Sovleplenib showed anti-tumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted.

Assessment of Prophylactic Internal Carotid Artery Management in Postradiation Nasopharyngeal Necrosis Patients.

OBJECTIVE: Postradiation nasopharyngeal necrosis (PRNN) frequently develops after second-course radiotherapy for nasopharyngeal carcinoma (NPC). PRNN can lead to internal carotid artery (ICA) massive hemorrhage due to ICA rupture, resulting in sudden death. This study aims to explore the pretreatment of the ICA to prevent fatal massive hemorrhage in PRNN patients. STUDY DESIGN: Retrospective cohort study. SETTING: Sun Yat-sen University Cancer Center. METHODS: Patients diagnosed with NPC and PRNN from January 2010 to September 2022 were included. The Cox proportional hazards regression analysis was performed to analyze risk factors for massive hemorrhage and survival. A nomogram was developed to integrate prognostic models and perform parameter calibration. RESULTS: Two hundred and fifty-four PRNN patients were included in this study. Prophylactic ICA occlusion significantly reduced the risk of ICA hemorrhage compared to no prophylactic ICA occlusion (3.6% vs 40.6%, P < .001). Surgical repair on necrosis significantly prevented hemorrhage and improved survival. The nomogram, incorporating the above 2 factors and the nearest distance from necrosis to ICA ≤ 3 mm, exhibited excellent discriminative ability for hemorrhage. We identified 3 high-risk factors that indicate the need for prophylactic ICA management in PRNN patients: (1) exposure of ICA by rhinoscopy; (2) signs of ICA erosion on MRA scanning; (3) the depth of soft tissue coverage surrounding the ICA wall within the necrotic cavity is less than 3 mm on magnetic resonance imaging. CONCLUSION: We have identified 3 high-risk factors for PRNN patients that necessitate prophylactic ICA management. These findings are expected to contribute to improving the quality of life and overall survival of PRNN patients.

Radiomics Prediction of Muscle Invasion in Bladder Cancer Using Semi-Automatic Lesion Segmentation of MRI Compared with Manual Segmentation.

Conventional radiomics analysis requires the manual segmentation of lesions, which is time-consuming and subjective. This study aimed to assess the feasibility of predicting muscle invasion in bladder cancer (BCa) with radiomics using a semi-automatic lesion segmentation method on T2-weighted images. Cases of non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa (MIBC) were pathologically identified in a training cohort and in internal and external validation cohorts. For bladder tumor segmentation, a deep learning-based semi-automatic model was constructed, while manual segmentation was performed by a radiologist. Semi-automatic and manual segmentation results were respectively used in radiomics analyses to distinguish NMIBC from MIBC. An equivalence test was used to compare the models' performance. The mean Dice similarity coefficients of the semi-automatic segmentation method were 0.836 and 0.801 in the internal and external validation cohorts, respectively. The area under the receiver operating characteristic curve (AUC) were 1.00 (0.991) and 0.892 (0.894) for the semi-automated model (manual) on the internal and external validation cohort, respectively (both p < 0.05). The average total processing time for semi-automatic segmentation was significantly shorter than that for manual segmentation (35 s vs. 92 s, p < 0.001). The BCa radiomics model based on semi-automatic segmentation method had a similar diagnostic performance as that of manual segmentation, while being less time-consuming and requiring fewer manual interventions.

Novel NIR-II fluorescent probes for biliary atresia imaging.

Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.

Efficacy of sequential chemoradiotherapy combined with toripalimab in de novo metastatic nasopharyngeal carcinoma: A phase II trial.

Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>104 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.

Investigating the impact of value congruence on work engagement in EFL teachers: the role of teacher enthusiasm.

Introduction: This research aimed to investigate the influence of value congruence on EFL (English as a Foreign Language) teachers' work engagement, with a focus on the mediating role of teacher enthusiasm. Methods: A sample of EFL teachers (N = 453) in China participated in the study. Data were collected using self-report measures, including the Value Congruence Scale, Teacher Enthusiasm Scale, and Work Engagement Scale. Structural equation modeling was employed to analyze the data and test the proposed model. Results: The results revealed that value congruence had a significant positive direct effect on work engagement. Furthermore, teacher enthusiasm was found to mediate the relationship between value congruence and work engagement. Discussion: These findings suggest that when EFL teachers perceive a congruence between their personal values and the values upheld by their educational institutions, they are more likely to experience higher levels of work engagement, and this relationship is partially explained by their level of enthusiasm. The study contributes to the understanding of the factors that influence EFL teachers' work engagement and highlights the importance of value congruence and teacher enthusiasm in fostering a positive work environment. These findings have implications for the development of interventions and practices aimed at enhancing EFL teachers' well-being and job satisfaction.

A Rulefit-based prognostic analysis using structured MRI report to select potential beneficiaries from induction chemotherapy in advanced nasopharyngeal carcinoma: A dual-centre study.

BACKGROUND AND PURPOSE: Structured MRI report facilitate prognostic prediction for nasopharyngeal carcinoma (NPC). However, the intrinsic association among structured variables is not fully utilised. This study aimed to investigate the performance of a Rulefit-based model in feature integration behind structured MRI report and prognostic prediction in advanced NPC. MATERIALS AND METHODS: We retrospectively enrolled 1207 patients diagnosed with non-metastatic advanced NPC from two centres, and divided into training (N = 544), internal testing (N = 367), and external testing (N = 296) cohorts. Machine learning algorithms including multivariate analysis, deep learning, Lasso, and Rulefit were used to establish corresponding prognostic models. The concordance indices (C- indices) of three clinical and six combined models with different algorithms for overall survival (OS) prediction were compared. Survival benefits of induction chemotherapy (IC) were calculated among risk groups stratified by different models. A website was established for individualised survival visualisation. RESULTS: Incorporating structured variables into Stage model significantly improved the prognostic prediction performance. Six prognostic rules with structured variables were identified by Rulefit. OS prediction of Rules model was comparable to Lasso model in internal testing cohort (C-index: 0.720 vs. 0.713, P = 0.100) and achieved the highest C-index of 0.711 in external testing cohort, indicating better generalisability. The Rules model stratified patients into risk groups with significant 5-year OS differences in each cohort, and revealed significant survival benefits from additional IC in high-risk group. CONCLUSION: The Rulefit-based Rules model, with the revelation of intrinsic associations behind structured variables, is promising in risk stratification and guiding individualised IC treatment for advanced NPC.

Association between specific ultrasound features of joints and impaired kidney function among gout patients.

OBJECTIVE: To investigate the relationship between the specific ultrasonic manifestations of lower limb joints and impaired kidney function in gouty arthritis. METHODS: In this cross-sectional study, 408 patients with gouty arthritis were divided into two groups based on the status of renal function: normal group (n = 240) and renal impairment (n = 168) group. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joints to detect ultrasound features of double-contour sign (DC) and tophus. Multiple logistic regression analysis was conducted to assess the association between kidney dysfunction and ultrasound features. A number of potential clinical confounders were adjusted in the model. RESULTS: Univariable conditional logistic regression produces several significant risk factors of impaired kidney function which were the highest and current lever of serum urate acid, course of disease, frequency of attack, hyperlipidemia, hypertension, diabetes, coronary heart disease, presence of multiple tophus, and DC (P < 0.05). After correcting the course of disease and other risk factors, tophus was still an independent risk factor of impaired kidney function and the multivariable adjusted odds ratios (95% CI) was 1.789 (1.005-3.185, P = 0.05), however, the association was not significant in DC (OR = 1.098, 95% CI: 0.668-1.803, P = 0.71). CONCLUSION: The ultrasound feature of tophus was associated with kidney dysfunction in patients with gout, independent of clinical risk factors, which may be helpful in guiding clinical practice.

Deep Semi-Supervised Ultrasound Image Segmentation by Using a Shadow Aware Network With Boundary Refinement.

Accurate ultrasound (US) image segmentation is crucial for the screening and diagnosis of diseases. However, it faces two significant challenges: 1) pixel-level annotation is a time-consuming and laborious process; 2) the presence of shadow artifacts leads to missing anatomy and ambiguous boundaries, which negatively impact reliable segmentation results. To address these challenges, we propose a novel semi-supervised shadow aware network with boundary refinement (SABR-Net). Specifically, we add shadow imitation regions to the original US, and design shadow-masked transformer blocks to perceive missing anatomy of shadow regions. Shadow-masked transformer block contains an adaptive shadow attention mechanism that introduces an adaptive mask, which is updated automatically to promote the network training. Additionally, we utilize unlabeled US images to train a missing structure inpainting path with shadow-masked transformer, which further facilitates semi-supervised segmentation. Experiments on two public US datasets demonstrate the superior performance of the SABR-Net over other state-of-the-art semi-supervised segmentation methods. In addition, experiments on a private breast US dataset prove that our method has a good generalization to clinical small-scale US datasets.

First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study.

BACKGROUND: This study aimed to compare the efficacy and safety of high-dose methotrexate (HD-MTX) versus teniposide (TEN) in patients with newly diagnosed immunocompetent primary central nervous system lymphomas (PCNSLs). METHODS: The study included immunocompetent, adult patients with newly diagnosed PCNSL at 22 centers in China from 2007 to 2016. The patients received HD-MTX or TEN as first-line induction therapy. The objective response rate, progression-free survival, and overall survival were analyzed for each patient cohort. RESULTS: A total of 96 patients were eligible: 62 received HD-MTX, while 34 received teniposide. The overall response rate was 73.2% and 72.7% in the MTX and the TEN cohorts, respectively (P = 0.627). The median progression-free survival was 28.4 months [95% confidence interval (CI): 13.7-51.2] in the MTX cohort and 24.3 months (95% CI: 16.6-32.1) in the TEN cohort (P = 0.75). The median overall survival was 31 months (95% CI: 26.8-35.2) in the MTX cohort and 32 months (95% CI: 27.6-36.4) in the TEN cohort (P = 0.77). The incidence of any grade of coagulopathy/deep-vein thrombosis and gastrointestinal disorders was significantly higher in the MTX cohort than in the TEN cohort; no significant difference was found in the incidence of other adverse events between the two cohorts. CONCLUSIONS: This was the first multicenter study using TEN as the main agent compared with HD-MTX in newly diagnosed primary CNS lymphoma. The TEN-based regimen was non-inferior to the HD-MTX-based regimen with similar overall responses. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that the teniposide-based regimen was non-inferior to high-dose methotrexate - based regimen with similar overall responses and long-time survival in immunocompetent patients with PCNSL.

Camrelizumab plus famitinib in patients with recurrent or metastatic nasopharyngeal carcinoma treated with PD-1 blockade: data from a multicohort phase 2 study.

Background: Treatment options for patients with recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) are not clear after progression on previous treatment with PD-(L)1 inhibitor; critical gaps in evidence remain for such cases. Immunotherapy combined with antiangiogenic therapy has been reported to have synergistic antitumor activity. Therefore, we evaluated the efficacy and safety of camrelizumab plus famitinib in patients with RM-NPC who failed treatment with PD-1 inhibitor-containing regimens. Methods: This multicenter, adaptive Simon minimax two-stage, phase II study enrolled patients with RM-NPC refractory to at least one line of systemic platinum-containing chemotherapy and anti-PD-(L)1 immunotherapy. The patient received camrelizumab 200 mg every 3 weeks and famitinib 20 mg once per day. The primary endpoint was objective response rate (ORR), and the study could be stopped early as criterion for efficacy was met (>5 responses). Key secondary endpoints included time to response (TTR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. This trial was registered with ClinicalTrials.gov, NCT04346381. Findings: Between October 12, 2020, and December 6, 2021, a total of 18 patients were enrolled since six responses were observed. The ORR was 33.3% (90% CI, 15.6-55.4) and the DCR was 77.8% (90% CI, 56.1-92.0). The median TTR was 2.1 months, the median DoR was 4.2 months (90% CI, 3.0-not reach), and the median PFS was 7.2 months (90% CI, 4.4-13.3), with a median follow-up duration of 16.7 months. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in eight (44.4%) patients, with the most common being decreased platelet count and/or neutropenia (n = 4, 22.2%). Treatment-related serious AEs occurred in six (33.3%) patients, and no deaths occurred due to TRAEs. Four patients developed grade ≥3 nasopharyngeal necrosis; two of them developed grade 3-4 major epistaxis, and they were cured by nasal packing and vascular embolization. Interpretation: Camrelizumab plus famitinib exhibited encouraging efficacy and tolerable safety profiles in patients with RM-NPC who failed frontline immunotherapy. Further studies are needed to confirm and expand these findings. Funding: Jiangsu Hengrui Pharmaceutical Co., Ltd.